Sponsor Attestation Checklist for Abbreviated New Drug Submissions (ANDS) and Supplements to an Abbreviated New Drug Submission (SANDS)

Locked files

Protected when completed.

Health Canada Use Only:
CR File Number:
Control Number:
Date/ Time of Receipt:

Sponsors should address the points outlined below by answering "Yes", "No",or "Not Applicable",providing a justification where required, and completing the requested information. For SANDSs, sponsors should only complete the applicable sections.

Introduction

Do you wish to receive communications from Health Canada regarding this submission via email?

• Yes
• No

Proposed Product:
Name of Drug Product:
Drug Substance(s):
Company (Sponsor) Name:
Dosage Form(s):
Strength(s):

Reference Product:
Name of Drug Product:
Drug Substance(s):
Company (Manufacturer):
Dosage Form(s):
Strength(s):

Module 1 - Administrative and Prescribing Information

Administrative Information

1.2.5 Compliance and Site Information
Has evidence been provided confirming that all facilities involved in fabricating, packaging or labelling, and testing of the drug product and manufacturing of a sterile drug substance received a Good Manufacturing Practice (GMP) compliance rating issued by the Health Products and Food Branch's (HPFB's) Inspectorate?

• Yes
• No

1.2.6 Authorization for Sharing Information
List Drug Master Files (DMF(s)) referenced (Type I - IV):

• Not Applicable

For the above DMFs:
1. Letters of Authorization provided?

• Yes
• No

2. DMF in order and up to date [for example (e.g.), fees paid]?

• Yes
• No

Has the sponsor verified whether or not a valid Certificate of Suitability (CEP) exists for this Active Pharmaceutical Ingredient (API) and manufacturing site/process?

• Yes
• No

If so, has the CEP been filed following advice posted in the current Therapeutic Products Directorate (TPD) communiqué?

• Yes
• No

1.2.7 International Information
Provide information on the product application filing or marketing status ("Mkd" = Marketed) of the proposed product in the following jurisdictions:

United States Food and Drug Administration (FDA):

• Filed
• Marketed

European Union (EU):

• Filed
• Marketed

If filed in the EU, indicate applicable procedure:

• Centralized
• De-Centralized
• Mutual Recognition
• National

Switzerland's Swiss Medic:

• Filed
• Marketed

Singapore's Health Sciences Authority (HSA):

• Filed
• Marketed

Australia's Therapeutic Goods Agency (TGA):

• Filed
• Marketed

Has Foreign Review Information for any of the above jurisdictions been provided?

• Yes
• No

If Yes, indicate which jurisdictions:

Module 3 - Quality

Drug Substance

S.1 General Information
Does the proposed active pharmaceutical ingredient comply with the definition of Pharmaceutical Equivalence as per the Food and Drug Regulations and the Interpretation of "Identical Medicinal Ingredient" Policy?

• Yes
• No

S.4 Control for the Drug Substance
Do any of the proposed limits for impurities exceed the applicable International Conference on Harmonisation (ICH) Qualification Threshold in Q3A?

• Yes
• No

For these impurities that are not qualified based on limits in an official compendial monograph, has a justification or toxicological assessment/studies been submitted?

• Yes
• No

Identify section where complete toxicity studies have been provided (e.g., Module 4):

Has each identified impurity been surveyed for structural alerts for potential genotoxic impurities?

• Yes
• No

Does the dossier clearly identify and discuss impurities that are potentially genotoxic?

• Yes
• No

If proposed limits for these impurities are above the Threshold of Toxicological Concern (TTC), has toxicological assessment/studies been submitted?

• Yes
• No

Location where complete toxicity studies have been provided (e.g., Module 4):

S.7 Stability
Have the minimum required stability data (2 batches, minimum pilot scale, 6 months long term, 6 months accelerated) been provided under ICH storage conditions?

• Yes
• No

If No, provide justification:

Drug Product

Batches used in comparative bioavailability study/ studies:

Test Product:
Strength:
Batch number:
Batch size:
Largest proposed commercial batch size:

Reference Product:
Strength:
Batch number:
Batch size:
Largest proposed commercial batch size:

Is the biobatch "pilot scale" (e.g. one-tenth of full production scale or 100,000 units, whichever is larger)?

• Yes
• No

If No, provide justification:

P.2 Pharmaceutical Development
Has justification been provided to support the request for waiver of biostudies?

• Yes
• No

For solid oral dosage forms: Have comparative dissolution profiles been provided for all generic strength(s) not used in a comparative bioavailability study against the generic strength for which bioequivalence was demonstrated?

• Yes
• No
• Not applicable

Has justification of the choice of dissolution method including discussion of the discriminatory power of the dissolution method been provided?

• Yes
• No

For solutions: Have results of comparisons of the test and reference products been provided (e.g., formulations, physicochemical properties)?

• Yes
• No

For dosage forms with delivery devices: Has a comparison of the physical and operating characteristics of the device attributes and performance of the delivery system been provided?

• Yes
• No

For tablets:
Is the second-entry product identical to the innovator's product with respect to scoring configuration?

• Yes
• No

If No, provide justification:

If the proposed product is scored, have results of a divisibility study been provided?

• Yes
• No

Location of results/study:

For the comparative bioavailability studies, was the reference product sourced from the Canadian market?

• Yes
• No

If a foreign sourced reference product was used, have the criteria outlined in the Canadian Reference Product policy been addressed?

• Yes
• No

Location of results/study:

Was the same lot of the foreign sourced reference product used in the comparative bioavailability studies and all in vitro comparative studies?

• Yes
• No

If No, provide justification:

P.2.4 Container Closure System
For liquids, solutions, and semi-solid products: Has a discussion or studies on Extractables/Leachables been provided for the drug product during shelf-life? (e.g., Extractable compounds inherent to the primary components of the container-closure system (CCS) which may leach into the drug product during stability)?

• Yes
• No

If No, provide justification:

Have results been provided for:

• Yes
• No

USP <381> Elastomeric Closures for Injections (includes USP <87>/<88> tests)

• Yes
• No

USP <661> Containers

• Yes
• No

USP <671> Containers-Permeation

• Yes
• No

P.2.6 Compatibility
For parenteral products: Have data been provided for ALL diluents over the concentration range, storage condition and storage time as specified in the Innovator's Product Monograph for the Canadian Reference Product (CRP)?

• Yes
• No
• Not applicable

If No, provide justification:

P.3.5 Process Validation and/or Evaluation
Has a process validation report been included with results performed on three consecutive, production-scale batches of the drug product?

• Yes
• No

If No, has a process validation protocol been submitted with a commitment that three consecutive, production-scale batches of the drug product will be subjected to prospective validation?

• Yes
• No

For parenteral products: Has the following documentation been provided:

Drug substance Bacterial Endotoxin test validation

• Yes
• No

Drug product Bacterial Endotoxin test validation

• Yes
• No

Validation for sterile filters

• Yes
• No

If Yes, specify report (e.g., Membrane Compatibility Test Report, Extractable Substances documentation):

Has the validation of sterilization process been conducted?

• Yes
• No

For aseptic sterilisation techniques, has a justification been provided for the use of aseptic processes versus terminal steam sterilization?

• Yes
• No
• Not applicable

If No, provide justification:

Has the validation of sterilization of packaging materials been conducted?

• Yes
• No

Has a study on the integrity of the container closure system been conducted?

• Yes
• No

P.5.6
Do any of the proposed limits for degradation products exceed the applicable ICH Qualification Threshold in ICH Q3B?

• Yes
• No

For these impurities that are not qualified based onlimits in anofficial compendial monograph, hasa justification or toxicological assessment/studies been submitted?

• Yes
• No

Identify sectionwhere complete toxicity studies have been provided (e.g. Module 4):

P.8 Stability
Have the minimum required stability data (6 months long term, 6 months accelerated) been provided under ICH storage conditions?

• Yes
• No

If No, provide justification:

Have stability data been provided on at least two unique batches of each strength at minimum pilot scale (e.g. one-tenth of full production scale or 100,000 units, whichever is larger)?

• Yes
• No

If No, provide justification:

Have stability data been provided in all types of container closure systems?

• Yes
• No

If No, provide justification:

Have the results of stress testing (e.g., including Photostability studies of the drug product) been provided?

• Yes
• No

Location of results/study:

If No, provide justification:

Regional Information

R.1.1 Executed Production Documents
Have a minimum of two batches for each strength been manufactured?

• Yes
• No

If No, provide justification:

Have copies of the executed production documents been provided for each strength (including the batches used in the pivotal clinical and/or comparative biostudies)?

• Yes
• No

Has the above been provided for all proposed manufacturing sites?

R 1.2 Master Production Documents
Have copies of the drug product master production documents been provided for each proposed strength, commercial batch size, and manufacturing site?

• Yes
• No

For parenteral products, have details of manufacturing processes (e.g., washing, treatment, sterilizing, and depyrogenating of containers, closures and equipment; filtration of solutions, final inspection of the product, and sterilization cycle) been provided, including referenced Standard Operating Procedures (SOPs) where applicable?

• Yes
• No

If No, provide justification:

Module 5 - Clinical Study Reports

Comparative Bioavailability Studies

List comparative bioavailability study or studies included in the submission:
The description should include study number, study design, products administered, dose and conditions of administration (e.g., 1 x 100 milligrams, fasting/fed).

For each study - Has justification been provided for the use of non-standard conditions of administration (e.g., fed instead of fasting conditions, modifications to test meal composition for studies conducted under fed conditions)?

• Yes
• No
• Not Applicable

Location of justification:

For each study - Is a waiver from the requirement to provide comparative bioavailability data under fed conditions requested?

• Yes
• No
• Not Applicable

For each study - If the study was conducted outside of Canada, provide a list of clinical and bioanalytical facilities employed:
The description should include the name and address of each facility.

For each study - Has documentation establishing the GCP compliance of the clinical and bioanalytical facilities to current FDA or ICH standards been provided?

• Yes
• No

Specifically, documentation should be provided to support the outcome(s) of inspection(s) of the sites by the FDA or an ICH Authority.  Note that documentation from the FDA should include all 482 and 483 Forms that were issued, the responses to the deficiencies noted on Form 483, as well as the Establishment Inspection Report.

Test Product

Are all strengths proportionally formulated to the strength administered in the comparative bioavailability study as per the criteria outlined in the Bioequivalence of Proportional Formulations policy?

• Yes
• No
• Not Applicable

Is a waiver of the requirement to provide comparative bioavailability data requested?

• Yes
• No

Justification for the waiver request is based on:

• Proportionality Policy?
  • Yes
  • No
• In-vitro in-vivo correlation based data?
  • Yes
  • No

Location of results/study:

Reference Product

Is the reference product sourced from the Canadian market?

• Yes
• No

If a foreign sourced reference product was used:
Have criteria outlined in the Canadian Reference Product policy been addressed?

• Yes
• No

Are reference product labels for the lot used in the comparative bioavailability studies provided, including manufacture date and lot number?

• Yes
• No

Bioanalytical Method

Analyte(s) measured:

• parent
• metabolite

Has justification been provided for basing bioequivalence on metabolite data instead of parent?

• Yes
• No
• Not Applicable

Has the bioanalytical report been provided?

• Yes
• No
• Not Applicable

Has the method validation report been provided?

• Yes
• No

If Yes, have long-term stability data to support analyte integrity for the longest period of subject sample storage (from the first day of sample collection to the last day of sample analysis) been provided?

• Yes
• No

Sponsor Attestation

I, the undersigned, certify that:

• The information and material included in this checklist is accurate and complete.
• No information is false or misleading and no omissions have been made that may affect its accuracy and completeness.

Name of Authorized Signing Official:
Signature:
Date (YYYY/MM/DD):
Company Name and Address:
Title:
Telephone Number:
Fax Number:
E-mail Address: